Reagent Friday: Sodium Periodate
Last updated: February 21st, 2020 |
Sodium Periodate, NaIO4 As A Reagent In Organic Chemistry
In organic chemistry, sometimes you need to build molecules up. Other times, you need to break molecules down. Ozone, which we talked about earlier, is a really useful reagent for that. Here’s another one, although it’s a little more obscure.
Sodium Periodate (NaIO4) Cleaves 1,2-Diols (“Vicinal” Diols) To Aldehydes And Ketones
Sodium periodate (NaIO4) breaks apart 1,2-diols (“vicinal” diols) to form aldehydes and ketones. In this respect it’s the same as periodic acid (HIO4) and lead tetra-acetate [Pb(OAc)4].
Notice what’s happening to NaIO4 here – it’s becoming reduced from iodine(VII) to iodine(V). In the process we’re cleaving a C-C bond and forming two C-O π bonds. Comes in handy sometimes, when you want to break apart an alkene and form aldehydes and ketones.
Cleavage Of Vicinal Diols By Sodium Periodate (NaIO4) – The Mechanism
The first step in cleavage of vicinal diols by NaIO4 is the direct attachment of the alcohols to the iodine. This occurs through two successive attacks of the iodine by lone pairs on each of the hydroxyl groups followed by a proton transfer.
In the second step, what happens is a kind of reverse cycloaddition (similar to what happens when an ozonide breaks down). This is a somewhat simplified version of the mechanism (skipping over the proton transfer). The key part here is the third diagram, where the cyclic iodate ester breaks down to give the ketone and aldehyde.
And there you go: aldehydes or ketones, depending on whether you’re breaking down secondary or tertiary alcohols (primary alcohols become formaldehyde). So this actually gives you a second way to cleave double bonds to alkenes/ketones besides ozone. You can take an alkene, treat it with osmium tetroxide (OsO4) first to make the diol, and then NaIO4 it. This is, incidentally, sometimes called “Johnson-Lemieux cleavage“. Obscure organic chemistry named reaction of the day!
P.S. You can read about the chemistry of NaIO4 and more than 80 other reagents in undergraduate organic chemistry in the “Organic Chemistry Reagent Guide”, available here as a downloadable PDF. The Reagents App is also available for iPhone, click on the icon below!
(Advanced) References and Further Reading
The most common oxidizing agents used for this reaction are KMnO4, periodic acid (Malaprade reaction), and Pb(OAc)4 (Criegee reaction).
- Malaprade, Bull. Soc. Chim. Fr. 3, 1, 833 1934
First paper on the oxidative cleavage of 1,2-diols, now also known as the Malaprade oxidation.
- Chemoselective hydrolysis of terminal isopropylidene acetals and subsequent glycol cleavage by periodic acid in one pot
Wenlian Wu and Yulin Wu
The Journal of Organic Chemistry 1993, 58 (13), 3586-3588
This can be considered a tandem or domino reaction – periodic acid unmasking a diol from an acetal and then oxidatively cleaving it in one pot.
- Eine oxydative Spaltung von Glykolen (II. Mitteil. über Oxydationen mit Blei(IV)‐salzen)
Ber. 1931, 64 (2), 260-266
The first paper by on the oxidation of 1,2-diols with Pb(IV) salts, by Rudolf Criegee.
- Direct Titration of cis-Glycols with Lead Tetraacetate
Analytical Chemistry 1949, 21 (6), 751-751
This reaction can also be used for the analytical quantification of 1,2-diols, as this paper describes.
- Lead Tetraacetate Oxidations in the Sugar Group. XI. The Oxidation of Sucrose and Preparation of Glycerol and Glycol
Robert C. Hockett and Morris Zief
Journal of the American Chemical Society 1950, 72 (5), 2130-2132
Pb(OAc)4 is commonly used as an oxidant in carbohydrate chemistry, as this paper describes. It is used to cleave 1,2-glycols and differentiate between different kinds of glycol groups.
- (1’R)-(−)-2,4-O-ETHYLIDENE-D-ERYTHROSE AND ETHYL (E)-(−)-4,6-O-ETHYLIDENE-(4S,5R,1’R)-4,5,6-TRIHYDROXY-2-HEXENOATE
Fengler-Veith, O. Schwardt, U. Kautz, B. Krämer, and V. Jäger
Org. Synth. 2002, 78, 123
A procedure in Organic Syntheses using NaIO4 oxidation in carbohydrate chemistry.